Methanol → (rac)-N-[4-(4-Cyanophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl]-N'-propylsulfuric diamide

HRID 714064Notes

Reaction equation

HRID 714064 reaction equation
[NH2:1][CH:2]1[C:11]2[CH:10]=[N:9][CH:8]=[C:7]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[C:6]=2[CH2:5][CH2:4][CH2:3]1.[CH2:20]([NH:23][S:24](Cl)(=[O:26])=[O:25])[CH2:21][CH3:22].CCN(CC)CC.CO>C(Cl)Cl>[C:16]([C:15]1[CH:14]=[CH:13][C:12]([C:7]2[C:6]3[CH2:5][CH2:4][CH2:3][CH:2]([NH:1][S:24](=[O:26])(=[O:25])[NH:23][CH2:20][CH2:21][CH3:22])[C:11]=3[CH:10]=[N:9][CH:8]=2)=[CH:19][CH:18]=1)#[N:17]

Participants

6

Reactant 4

HCID 887MethanolHCID 8471Triethylamine2×HCID 13398949N-propylsulfamoyl chlorideHCID 718113604-(8-Amino-5,6,7,8-tetrahydro-4-isoquinolinyl)benzonitrile

Product 1

HCID 71811362(rac)-N-[4-(4-Cyanophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl]-N'-propylsulfuric diamideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A cooled (0° C.) solution of (rac)-4-(8-amino-5,6,7,8-tetrahydroisoquinolin-4-yl)benzonitrile (example 1) (62.3 mg, 250 μmol) in CH2Cl2 (3 ml) was treated with propylsulfamoyl chloride (98.5 mg, 625 μmol) in CH2Cl2 (0.6 ml) and Et3N (69.7 μL, 500 μmol). After 1 h the mixture was stirred at room temperature for 1 h, cooled down (0° C.) and treated again with Et3N (69.7 μL, 500 μmol). After ½ h at room temperature, the mixture was treated with MeOH (0.2 mL) and extracted with water/AcOEt (3×). The organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane gave the title compound (63 mg, 68%) as off-white powder. MS: 371.2 (M+H+).

Workup

  1. temperaturecooled down (0° C.)
  2. waitAfter ½ h at room temperature
  3. extractionextracted with water/AcOEt (3×)
  4. dry with materialThe organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customPurification
  8. customby flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 3%)) and precipitation from CH2Cl2 with n-pentane

Sources & evidence

ORD record
ord-beee2114ca484373af676d4505643951
Source dataset
uspto-grants-2015_11
Patent number
US09187429B2

Reaction notes

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